This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gonzalez, A. Articles by Ruiz, A. Search for Related Content PubMed PubMed Citation Articles by Gonzalez, A. Articles by Ruiz, A.

Specific CAPN10 Gene Haplotypes Influence the Clinical Profile of Polycystic Ovary Patients

Centro Avanzado de Fertilidad (CAF) (A.G., E.A., A.Ro., M.J.A., M.J.F., P.V., O.F.), Unidad de Reproducción y Genética Humana, Instituto Medico Serman, 11405 Jerez de la Frontera, Cádiz, Spain; Unidad Materno-Infantil (A.G.), Hospital Virgen de las Montañas, 11650 Villamartin, Cádiz, Spain; Dpto. Genómica Estructural (R.R., J.J.G., L.M.R., A.Ru.), neoCodex, 41020 Sevilla, Spain; and Servicio de Obstetricia y Ginecología (J.A.H.), Hospital SAS, 11403 Jerez de la Frontera, Spain

Address all correspondence and requests for reprints to: Dr. Alejandro González, Centro Avanzado de Fertilidad, Unidad de Reproducción y Genética Humana, Instituto Medico Serman, Jerez de la Frontera, Cádiz, Spain. E-mail: alejandro{at}caf-jerez.com.

Recently, several research groups have evaluated CAPN10 gene in polycystic ovarian syndrome (PCOS) patients and other phenotypes, including hirsutism or intermediate phenotypes of PCOS. Molecular genetic analysis of CAPN10 gene indicates that different alleles may play a role in PCOS susceptibility and could be associated with idiopathic hirsutism. However, these observations are not exempt from controversy, because independent studies cannot replicate these preliminary findings.

We present a haplotype-phenotype correlation study of CAPN10 haplotypes in 148 women showing ecographically detected polycystic ovaries (PCO) combined with one or more of these clinical symptoms: amenorrhea or severe oligomenorrhea, hyperandrogenism, and anovulatory infertility, as well as 93 unrelated controls. We have reconstructed and analyzed 482 CAPN10 haplotypes in patients and controls. We detected the association of UCSNP-44 allele with PCO phenotype in the Spanish population (P = 0.02). In addition, we identified several CAPN10 alleles associated to phenotypic differences observed between PCO patients, such as the presence of hypercholesterolemia (haplotype 1121, P = 0.005), presence of hyperandrogenic features (P = 0.05), and familial cancer incidence (haplotype 1111, P = 0.0005). Our results confirm the association of UCSNP-44 allele with PCO phenotype in the Spanish population. Moreover, we have identified novel candidate risk alleles and genotypes, within CAPN10 gene, that could be associated with important phenotypic and prognosis differences observed in PCOS patients.

NeoCodex have been partially funded by the Ministerio de Ciencia y Tecnología of Spain (FIT-010000-2002-43, FIT-010000-2002-64, and PTQ-2002-0206).

Abbreviations: PCO, Polycystic ovaries; PCOS, polycystic ovarian syndrome; SNP, single nucleotide polymorphisms; T, testosterone; T2DM, type 2 diabetes mellitus.

This article has been cited by other articles:

				M. Simoni, C.B. Tempfer, B. Destenaves, and B.C.J.M. Fauser Functional genetic polymorphisms and female reproductive disorders: Part I: polycystic ovary syndrome and ovarian response Hum. Reprod. Update, September 1, 2008; 14(5): 459 - 484. [Abstract] [Full Text] [PDF]

				M. Urbanek, S. Sam, R. S. Legro, and A. Dunaif Identification of a Polycystic Ovary Syndrome Susceptibility Variant in Fibrillin-3 and Association with a Metabolic Phenotype J. Clin. Endocrinol. Metab., November 1, 2007; 92(11): 4191 - 4198. [Abstract] [Full Text] [PDF]

				C. Vollmert, S. Hahn, C. Lamina, C. Huth, M. Kolz, A. Schopfer-Wendels, K. Mann, F. Bongardt, J. C. Mueller, F. Kronenberg, et al. Calpain-10 variants and haplotypes are associated with polycystic ovary syndrome in Caucasians Am J Physiol Endocrinol Metab, March 1, 2007; 292(3): E836 - E844. [Abstract] [Full Text] [PDF]

				A. Gonzalez, M.E. Saez, M.J. Aragon, J.J. Galan, P. Vettori, L. Molina, C. Rubio, L.M. Real, A. Ruiz, and R. Ramirez-Lorca Specific haplotypes of the CALPAIN-5 gene are associated with polycystic ovary syndrome Hum. Reprod., April 1, 2006; 21(4): 943 - 951. [Abstract] [Full Text] [PDF]

				E. Diamanti-Kandarakis and C. Piperi Genetics of polycystic ovary syndrome: searching for the way out of the labyrinth Hum. Reprod. Update, November 1, 2005; 11(6): 631 - 643. [Abstract] [Full Text] [PDF]

				H. F. Escobar-Morreale, M. Luque-Ramirez, and J. L. San Millan The Molecular-Genetic Basis of Functional Hyperandrogenism and the Polycystic Ovary Syndrome Endocr. Rev., April 1, 2005; 26(2): 251 - 282. [Abstract] [Full Text] [PDF]

				D. A. Ehrmann Polycystic Ovary Syndrome N. Engl. J. Med., March 24, 2005; 352(12): 1223 - 1236. [Full Text] [PDF]